Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA235177 | ENA |
REPOSITORIES: ENA
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Project description:Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors, however its toxicity and side-effect limits its clinical efficacy. Herein, the docetaxel-loaded solid lipid nanoparticles (DSNs) were developed to reduce systemic toxicity while still keeping its anti-cancer activity. To evaluate its anti-cancer activity and toxicity and understand the molecular mechanisms of DSNs, different cellular, molecular and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel-Taxotere and induced more apoptosis at 24 h treatment in vitro. It can cause the treated cancer cells arrested at G2/M phase in a dose-depend manner as Taxotere. The DSNs can also suppress tumor growth very effectively in a murine breast cancer model. Systemic analysis of gene expression profiles by microarray and the following verification experiments suggested that both DSNs and Taxotere regulate expression of series genes and these genes functions involved in DNA replication, DNA damage response, cell proliferation, apoptosis and cell cycle regulation. Some of these genes expressed differentially at protein level although their transcription level was similar under TAX and DSNs treatment. Moreover, DSNs improved main side-effect of Taxotere by greatly lowering myelosuppression toxicity to bone marrow cells from mice. Taken together, our results expound the anti-tumor efficacy and the potential working mechanisms of DSNs in its anti-cancer activity and toxicity, which provide a theoretical foundation to develop and apply more efficient docetaxel formulation to treat cancer patients.
2014-12-31 | GSE54091 | GEO
Project description:Transcriptomic changes induced by Curcumin loaded solid nanoparticles and radiation in breast cells
| PRJNA489291 | ENA
Project description:In breast cancer (BC) care, radiotherapy is considered an efficient treatment. However, approximately 90% of BC-related deaths are due to the metastatic tumor progression. Then, it is strongly desirable to improve tumors radiosensitivity using molecules with synergistic action. In this study, we developed curcumin-loaded solid nanoparticles (Cur-SLN) in order to increase curcumin bioavailability and evaluated their radiosensitizing ability in comparison to curcumin free (Cur), by using an in vitro approach on BC models. Precisely, here we analyzed the transcriptomic profiles induced by Cur-SLN treatments, in non tumorigenic MCF10A and tumorigenic MCF7 and MDA-MB-231 BC cell lines, highlighting the networks responsible of its radiosensitization ability. Curcumin loaded- SLN can be suggested in future preclinical and clinical studies to test its concomitant use during radiotherapy treatments with the double implications of being a radiosensitizing molecule against cancer cells, with a protective role against IR side effects.
2019-08-20 | GSE118061 | GEO
Project description:To further study the transcriptome of Caco-2 human colon epithelial-like cells after exposure to S-nitrosoglutathione (GSNO, 1.4 μM), or Eudragit RL PO polymeric nanoparticles (NP-ERL, 50 μg/mL) or GSNO loaded nanoparticles (NP-GSNO, 50 μg/mL corresponding to (1.4 μM GSNO) we investigate whole genome microarray to identify genes regulates by exposure or not to GSNO (1.4 μM) or Eudragit RL PO polymeric nanoparticles (NP-ERL, 50 μg/mL) or GSNO loaded nanoparticles (NP-GSNO, 50 μg/mL corresponding to (1.4 μM GSNO).
2015-12-31 | GSE69551 | GEO
Project description:To further study the transcriptome of THP-1 human monocytes after exposure to S-Nitrosoglutathione (GSNO), we investigate whole genome microarray expression to identify genes regulated by exposure or not to GSNO. To further study the transcriptome of THP-1 human monocytes after exposure for 4 h to 50 ug / mL of S-Nitrosoglutathione-loaded polymeric Eudragit RL nanoparticles (GSNO-loaded ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 50 ug / mL of GSNO-loaded ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 4 h to 200 ug / mL of empty polymeric Eudragit RL nanoparticles (empty ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 200 ug / mL of empty ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 24 h to 50 ug / mL of S-Nitrosoglutathione-loaded polymeric Eudragit RL nanoparticles (GSNO-loaded ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 50 ug / mL of GSNO-loaded ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 24 h to 50 ug / mL of empty polymeric Eudragit RL nanoparticles (empty ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 50 ug / mL of empty ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 4 h to 50 ug / mL of empty polymeric Eudragit RL nanoparticles (empty ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 50 ug / mL of empty ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 4 h to 200 ug / mL of S-Nitrosoglutathione-loaded polymeric Eudragit RL nanoparticles (GSNO-loaded ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 200 ug / mL of GSNO-loaded ENP.
2013-12-19 | GSE51186 | GEO
Project description:Among microtubule-targeting agents, docetaxel has received recent interest owing to its good therapeutic index. Clinical trials have underlined its potential for the treatment of advanced breast cancer, although little is known about its molecular mode of action in this context. We characterized the molecular changes induced by docetaxel in two well-known human breast carcinoma cell lines. Two mechanisms of action according to drug concentration were suggested by a biphasic sensitivity curve, and were further validated by cell morphology, cell cycle and cell death changes. Two to four nanomolar docetaxel induced aberrant mitosis followed by late necrosis, and 100 nM docetaxel induced mitotic arrest followed by apoptosis. Passing through mitosis phase was a requirement for hypodiploidy to occur, as shown by functional studies in synchronized cells and by combining docetaxel with the proteasome inhibitor MG132. Transcriptional profiling showed differences according to cell line and docetaxel concentration, with cell cycle, cell death and structural genes commonly regulated in both cell lines. Although p53 targets were mainly induced with low concentration of drug in MCF7 cells, its relevance in the dual mechanism of docetaxel cytotoxicity was ruled out by using an isogenic shp53 cell line. Many of the genes shown in this study may contribute to the dual mechanism by which docetaxel inhibits the growth of breast cancer cells at different concentrations. These findings provide a basis for rationally enhancing docetaxel therapy, considering lower concentrations, and better drug combinations. Keywords: Dose-response analysis
2007-02-09 | GSE5149 | GEO
Project description:Purpose: To determine whether docetaxel therapy of advanced prostate cancer can be improved by using docetaxel in combination with Aneustat (OMN54), a multivalent botanical drug candidate undergoing a Phase-I Clinical Trial, and to identify the molecular action of this drug combination. Experimental Design: Human metastatic, androgen-independent C4-2 prostate cancer cells and NOD-SCID mice bearing PTEN-deficient, metastatic and PSA-secreting, patient-derived subrenal capsule LTL-313H prostate cancer tissue xenografts were treated with docetaxel and Aneustat, either alone or in combination. Culture growth (at 48 hours) and xenograft size (at 3 weeks) were determined and animal health monitored. Xenografts were gene expression profiled using gene expression microarrays. Androgen receptor (AR) expression and AKT phosphorylation were examined. Results: Aneustat markedly inhibited C4-2 cell replication in a dose-dependent manner in vitro, reducing AR expression and AKT phosphorylation. Aneustat was not as effective as docetaxel in inhibiting LTL-313H xenograft growth. When combined, Aneustat and docetaxel markedly and synergistically enhanced anti-tumor activity without inducing major host toxicity, even leading to complete growth inhibition and tumor shrinkage not obtained with the single drugs. AR expression and AKT signalling in the xenografts were inhibited by docetaxel+Aneustat, but not by the single agents. Expression microarray analysis indicated that docetaxel+Aneustat led to expanded anticancer activity, in particular to targeting of cancer hallmarks that were not affected by the drugs on their own. Conclusion: Our findings, obtained with a clinically relevant prostate cancer model, suggest, for the first time, that docetaxel-based therapy of advanced human prostate cancer may be improved by combining docetaxel with Aneustat.
2014-10-23 | GSE48667 | GEO
Project description:To further study the transcriptome of Caco-2 human colon epithelial-like cells after exposure to S-nitrosoglutathione (GSNO, 1.4 μM), or Eudragit RL PO polymeric nanoparticles (NP-ERL, 50 μg/mL) or GSNO loaded nanoparticles (NP-GSNO, 50 μg/mL corresponding to (1.4 μM GSNO) we investigate whole genome microarray to identify genes regulates by exposure or not to GSNO (1.4 μM) or Eudragit RL PO polymeric nanoparticles (NP-ERL, 50 μg/mL) or GSNO loaded nanoparticles (NP-GSNO, 50 μg/mL corresponding to (1.4 μM GSNO). Changes in gene expression in Caco-2 cells incubated without (control) or with GSNO or nanoparticles for 4 h, were measured. Four biological replicates were performed as controls: S46_1_4 ; S46_1_3 ; S35_1_4 ; S35_1_3. Four biological replicates were performed for each conditions : wtih GSNO (1.4 µM) exposed cells (S46_2_2 ; S46_2_1 ; S35_2_2 ; S35_2_1), with NP-ERL (50 μg/mL) exposed cells (S46_1_2 ; S46_1_1 ; S35_1_2 ; S35_1_1) with NP-GSNO (50 μg/mL corresponding to 1.4 µM GSNO) exposed cells (S46_2_4 ; S46_2_3 ; S35_2_4 ; S35_2_3)
2015-12-31 | E-GEOD-69551 | biostudies-arrayexpress
Project description:The microarray results showed that linalool sitimulation of lipid-loaded HepG2 cells rewired the hepatic transcriptome profile, with linalool being comparable to those of fenofibrate. Total of 8,988 genes that were commonly and significantly expressed in all experimental groups, including control hepatocytes, lipid-loaded hepatocytes, and lipid-loaded hepatocyted stimulated with linalool or fenofibrate, respectively, to compare the transcriptome profile of linalool (1mM) with those of hypotriglyceridemic drug, fenofibrate (100 ?M). Lipid loading of hepatocytes notably changed hepatic transcriptome profile, where 77 % of the selected genes showed >20% changes in expression (fold change > 1.2 or fold change <0.8). However, linalool stimulation of lipid-loaded cells showed that 48 % of the selected genes had expression changes of >20%. Thus, 29 % of the selected genes became to show less than 20% changes in expression after linalool stimulation compared to the lipid-loaded condition. Fenofibrate showed 46 % of the selected gene expression changes of >20%. Thus, 31 % of the seleted genes fell into the <20% change category compared to the lipid-loaded condition after fenofibrate stimulation. Untreated control vs. lipid-loaded HepG2 cells (3 biological replicates), untreated control vs. lipid-loaded HepG2 cells treated with fenofibrate (3 biological replicates), untreated control vs. lipid-loaded HepG2 cells treated with linalool (2 biological replicates). One replicate per array
2013-04-11 | E-GEOD-45961 | biostudies-arrayexpress
Project description:Tumor associated macrophages (TAMs) are known to play a role in a multitude of processes that facilitate lung cancer growth, including the suppression of tumoricidal immune activation and the absorption of chemotherapeutics. Therefore, deciphering new therapies to reprogram TAMs towards an anti-tumor phenotype is at the cutting-edge of therapy development. The presence of iron-loaded macrophages has been associated with a better prognosis in lung cancer patients. Iron accumulation in macrophages stimulates pro-tumoricidal macrophage activity that triggers cytotoxic T-cell responses in the tumor microenvironment. In this study, we propose super-paramagnetic iron oxide nanoparticles (SPIONs) as a promising anti-lung cancer adjuvant therapy to reduce tumor cell growth. We used SPIONs to target iron to macrophages and observed that SPION-loaded macrophages reduced tumor cell growth due to the oxidative stress. Additionally, we found that SPIONs completely rewire the tumor microenvironment in mice towards an anti-tumor state and that in combination with crizotinib, a lung cancer targeted therapy, SPIONs show an additive effect in decelerating tumor growth
2024-04-18 | PXD040145 | Pride